LeukemiaPhase 1NCT00124644
Combination Chemotherapy and Tipifarnib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
A Phase 1 study testing cytarabine, daunorubicin hydrochloride and etoposide in people with Leukemia, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as cytarabine, daunorubicin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 to 59 years
- Conditions the study is for
- Leukemia
- What is being tested?
- cytarabine, daunorubicin hydrochloride and etoposide
- Type of treatment
- Surgery or procedure
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2006to Jan 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 59 years
- All sexes
- No healthy volunteers
- Adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed acute myeloid leukemia (AML) according to the WHO classification system
- High-risk disease
- Newly diagnosed disease
- Patients with secondary AML due to prior chemotherapy for a different malignancy are eligible
- No known inv(16), t(8;21), or t(15;17) cytogenetic abnormality
- No acute promyelocytic leukemia
- No CNS leukemia
PATIENT CHARACTERISTICS:
Age
- 18 to 59
Performance status
- ECOG 0-2
Life expectancy
- More than 6 months
Hematopoietic
- Not specified
Hepatic
- AST and ALT ≤ 2.5 times upper limit of normal
- Bilirubin normal
Renal
- Creatinine normal OR
- Creatinine clearance ≥ 60 mL/min
Cardiovascular
- Ejection fraction > 50% by echocardiogram or MUGA
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
Immunologic
- No known HIV positivity
- No history of allergic reactions attributed to compounds of similar chemical or biological composition to tipifarnib
- No allergy to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)
- No ongoing or active infection
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other uncontrolled illness
- No psychiatric illness or social situation that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent epoetin alfa
Chemotherapy
- See Disease Characteristics
- No prior chemotherapy for AML or myelodysplastic syndromes except hydroxyurea
Endocrine therapy
- Not specified
Radiotherapy
- No concurrent palliative radiotherapy
Surgery
- Not specified
Other
- More than 30 days since prior investigational agents
- No other concurrent investigational or commercial agents or therapies for the malignancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, 43210-1240
About this study
Official title: A Phase I Study of R115777 (Zarnestra) in Combination With Induction Chemotherapy in Patients With Newly Diagnosed, High Risk Acute Myeloid Leukemia
RATIONALE: Drugs used in chemotherapy, such as cytarabine, daunorubicin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with tipifarnib may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given together with combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia.
Read the detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of tipifarnib when given in combination with induction therapy comprising cytarabine, daunorubicin, and etoposide followed by consolidation therapy comprising high-dose cytarabine in patients with newly diagnosed high-risk acute myeloid leukemia.
Secondary
- Determine the qualitative and quantitative toxic effects of this regimen, in terms of organ specificity, time course, predictability, and reversibility, in these patients.
- Determine the rate of complete remission in patients treated with this regimen.
- Determine the remission duration, overall survival, and relapse-free and event-free survival of patients treated with this regimen.
- Determine the pharmacokinetics of this regimen in these patients.
- Correlate pharmacodynamic measurements and levels of tumor necrosis factor-alpha with clinical response in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of tipifarnib.
- Induction therapy: Patients receive cytarabine IV continuously on days 1-7; daunorubicin IV and etoposide IV over 2 hours on days 5-7; and oral tipifarnib twice daily on days 5-12.
Patients undergo bone marrow biopsy on day 17 OR days 17 and 24 (if day 17 bone marrow biopsy shows suspicious disease). Patients achieving a complete remission (CR) proceed to consolidation therapy. Patients with residual disease, defined as > 5% leukemic blasts in a bone marrow of ≥ 20% cellularity, receive a second course of induction therapy comprising cytarabine IV continuously on days 1-5; daunorubicin IV and etoposide IV over 2 hours on days 4 and 5; and oral tipifarnib twice daily on days 4-9. Patients achieving a CR after a second course of induction therapy proceed to consolidation therapy. Patients not achieving a CR after a second course of induction therapy are removed from the study.
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 12 patients are treated at the MTD.
- Consolidation therapy: Patients receive high-dose cytarabine IV twice daily on days 1, 3, and 5. Treatment repeats approximately every 6-8 weeks for 4 courses.
After completion of study treatment, patients are followed every 3-6 months for up to 5 years.
PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 10-15 months.
- Conditions
- Leukemia
- Being tested
- cytarabine, daunorubicin hydrochloride, etoposide, tipifarnib, chemotherapy
- Keywords
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(16;16)(p13;q22), untreated adult acute myeloid leukemia, secondary acute myeloid leukemia
- Medical subject headings
- Leukemia, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cytarabineDrug
daunorubicin hydrochlorideDrug
etoposideDrug
tipifarnibDrug
chemotherapyProcedure or surgery
enzyme inhibitor therapyProcedure or surgery
high-dose chemotherapyProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2005 (estimated)
- Study startMar 2006
- Primary completionDec 2007
- Study completionJan 2008
Why it stopped: Withdrawn due to "toxicity" problems
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Ohio State University Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 30 participants
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- William G. Blum, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00124644
- Sponsor's protocol ID
- CDR0000437105
- Other IDs
- OSU-05020, OSU-2005C0024, NCI-6623
- Status last verified
- Jan 2008
- First submitted
- 26 Jul 2005
- Last updated
- 3 May 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of R115777 (Zarnestra) in Combination With Induction Chemotherapy in Patients With Newly Diagnosed, High Risk Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT00124644
- Acronym / sponsor ID
- CDR0000437105
- Conditions
- Leukemia
- Keywords
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(16;16)(p13;q22), untreated adult acute myeloid leukemia, secondary acute myeloid leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Withdrawn due to "toxicity" problems
- Enrolment
- 30 participants
- Lead sponsor
- Ohio State University Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2006
- Primary completion
- Dec 2007 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 28 Jul 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as cytarabine, daunorubicin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with tipifarnib may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given together with combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia.
Detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of tipifarnib when given in combination with induction therapy comprising cytarabine, daunorubicin, and etoposide followed by consolidation therapy comprising high-dose cytarabine in patients with newly diagnosed high-risk acute myeloid leukemia.
Secondary
- Determine the qualitative and quantitative toxic effects of this regimen, in terms of organ specificity, time course, predictability, and reversibility, in these patients.
- Determine the rate of complete remission in patients treated with this regimen.
- Determine the remission duration, overall survival, and relapse-free and event-free survival of patients treated with this regimen.
- Determine the pharmacokinetics of this regimen in these patients.
- Correlate pharmacodynamic measurements and levels of tumor necrosis factor-alpha with clinical response in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of tipifarnib.
- Induction therapy: Patients receive cytarabine IV continuously on days 1-7; daunorubicin IV and etoposide IV over 2 hours on days 5-7; and oral tipifarnib twice daily on days 5-12.
Patients undergo bone marrow biopsy on day 17 OR days 17 and 24 (if day 17 bone marrow biopsy shows suspicious disease). Patients achieving a complete remission (CR) proceed to consolidation therapy. Patients with residual disease, defined as > 5% leukemic blasts in a bone marrow of ≥ 20% cellularity, receive a second course of induction therapy comprising cytarabine IV continuously on days 1-5; daunorubicin IV and etoposide IV over 2 hours on days 4 and 5; and oral tipifarnib twice daily on days 4-9. Patients achieving a CR after a second course of induction therapy proceed to consolidation therapy. Patients not achieving a CR after a second course of induction therapy are removed from the study.
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 12 patients are treated at the MTD.
- Consolidation therapy: Patients receive high-dose cytarabine IV twice daily on days 1, 3, and 5. Treatment repeats approximately every 6-8 weeks for 4 courses.
After completion of study treatment, patients are followed every 3-6 months for up to 5 years.
PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 10-15 months.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cytarabine | Drug | – |
| daunorubicin hydrochloride | Drug | – |
| etoposide | Drug | – |
| tipifarnib | Drug | – |
| chemotherapy | Procedure or surgery | – |
| enzyme inhibitor therapy | Procedure or surgery | – |
| high-dose chemotherapy | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
Results and safety
The study was stopped early (reason given: Withdrawn due to "toxicity" problems). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2013.
Related trials for Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William G. Blum, MD principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing cytarabine, daunorubicin hydrochloride and etoposide in people with Leukemia, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Withdrawn due to "toxicity" problems). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2013.